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Theranostics 2023; 13(4):1289-1301. doi:10.7150/thno.80054 This issue Cite

Research Paper

Human circulating small non-coding RNA signature as a non-invasive biomarker in clinical diagnosis of acute myeloid leukaemia

Lin Xia^1*, Huanping Guo^1*, Xiao Wu^1*, Yinying Xu^1*, Pan Zhao^1*, Bingbing Yan¹, Yunjing Zeng¹, Yundi He¹, Dan Chen¹, Robert Peter Gale², Yunfang Zhang^3✉, Xi Zhang^1,4✉

1. Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China.
2. Haematology Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
3. Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
4. Jinfeng Laboratory, Chongqing, China
* These authors contributed equally to this work.

✉ Corresponding authors: Xi Zhang, Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China; Jinfeng Laboratory, Chongqing, 401329, China. Tel: +86-023-68783496; Email: zhangxxicom. Yunfang Zhang, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. Tel: +86-18810085579; Email: zhangyunfangedu.cn. More

Abstract

Background: Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults; AML is highly heterogeneous and involves abnormalities at multiple omics levels. Small non-coding RNAs (sncRNAs) present in body fluids are important regulatory molecules and considered promising non-invasive clinical diagnostic biomarkers for disease. However, the signature of sncRNA profile alteration in AML patient serum and bone marrow supernatant is still under exploration.

Methods: We examined data for blood and bone marrow samples from 80 consecutive, newly-diagnosed patients with AML and 12 healthy controls for high throughput small RNA-sequencing. Differentially expressed sncRNAs were analysed to reveal distinct patterns between AML patients and controls. Machine learning methods were used to evaluate the efficiency of specific sncRNAs in discriminating individuals with AML from controls. The altered expression level of individual sncRNAs was evaluated by RT-PCR, Q-PCR, and northern blot. Correlation analysis was employed to assess sncRNA patterns between serum and bone marrow supernatant.

Results: We identified over 20 types of sncRNA categories beyond miRNAs in both serum and bone marrow supernatant, with highly coordinated expression patterns between them. Non-classical sncRNAs, including rsRNA (62.86%), ysRNA (14.97%), and tsRNA (4.22%), dominated among serum sncRNAs and showed sensitive alteration patterns in AML patients. According to machine learning-based algorithms, the tsRNA-based signature robustly discriminated subjects with AML from controls and was more reliable than that comprising miRNAs. Our data also showed that serum tsRNAs to be closely associated with AML prognosis, suggesting the potential application of serum tsRNAs as biomarkers to assist in AML diagnosis.

Conclusions: We comprehensively characterized the expression pattern of circulating sncRNAs in blood and bone marrow and their alteration signature between healthy controls and AML patients. This study enriches research of sncRNAs in the regulation of AML, and provides insights into the role of sncRNAs in AML.

Keywords: human circulating sncRNA, tsRNA, ysRNA, rsRNA, alternative noninvasive biomarker

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